title: Transcutaneous delivery of tetanus toxin Hc fragment induces superior tetanus toxin neutralizing antibody response compared to tetanus toxoid.
abstract: Transcutaneous immunization is a promising vaccination delivery strategy which targets potent immune cells residing in the outer layer of the skin. In this study, the immunogenicity and neutralizing potency of the non-toxic Hc fragment of tetanus toxin (HcWT) and a mutant of Hc lacking ganglioside binding activity were compared with that of tetanus toxoid (TTxd) following transcutaneous immunization (TCI) of mice. Mice immunized with HcWT in the absence of an adjuvant induced highest anti-toxoid and anti-Hc antibody titres, with a significant increase in the toxin neutralizing antibody response compared with TTxd. These results are in contrast to previous studies employing subcutaneous delivery, where TTxd was found to be a more potent immunogen than the Hc fragment of the toxin. We conclude that the HcWT protein is more immunogenic than TTxd when given via the transcutaneous route. Our results suggest that TCI may provide an opportunity for effective delivery of toxin-like antigens which harbor protective epitopes and that traditional toxoid proteins may not be optimal antigens for skin immunization.
authors.affiliation: Division of Bacteriology, National Institute for Biological Standards and Control, Hertfordshire, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Johnston
authors.forename: Fatme
authors.initials: F
authors.lastname: Mawas
authors.forename: Rob
authors.initials: R
authors.lastname: Tierney
authors.forename: Omar
authors.initials: O
authors.lastname: Qazi
authors.forename: Neil
authors.initials: N
authors.lastname: Fairweather
authors.forename: Dorothea
authors.initials: D
authors.lastname: Sesardic
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000992:Antitoxins / Q000097:blood*; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000276:immunology*; D013744:Tetanus Toxin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000276:immunology*; D013745:Tetanus Toxoid / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D000992:Antitoxins; D007074:Immunoglobulin G; D010446:Peptide Fragments; D013744:Tetanus Toxin; D013745:Tetanus Toxoid; C040635:tetanus toxin fragment C